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Evolution of the Ebola Virus
History Ebola virus disease, also known as Ebola hemorrhagic fever, made its first appearance in 1976 with 2 simultaneous outbreaks in Nzara, Sudan and the Democratic Republic of Congo, near the Ebola River from which the disease was named. No further outbreaks were reported in Africa until 1994 and since then the disease has appeared in humans in eight different outbreaks. Ebola virus disease. from http://www.who.int/mediacentre/factsheets/fs103/en/ This disease is severe and often fatal in humans with an average fatality rate reported by the World Health Organization of nearly 50%, although rates from individual outbreaks have ranged from 25% to 90% depending on the severity of the outbreak. Leroy,Eric M., et al. "[http://www.sciencemag.org/content/303/5656/387.short Multiple Ebola virus transmission events and rapiddecline of central African wildlife]." ''Science'' 303.5656 (2004):387-390. Outbreaks generally occur suddenly with the source of the outbreak being extremely hard to pinpoint. However, it has been confirmed that many times when the disease reappears, it has been transmitted to humans through other animals (gorilla, chimpanzee, or duiker) with the disease by ingesting or coming into contact with the meat/animal fluids. Once in humans, the disease can then be transmitted from person to person, usually first infecting an entire family and then branching out to others. Viral Evolution During an outbreak, it is important to try and determine the source of the disease and to also determine if all patients follow the same epidemic chain.Dowell, Scott F., et al. "[http://jid.oxfordjournals.org/content/179/Supplement_1/S87.short Transmission of Ebola hemorrhagic fever: a study of risk factors in family members, Kikwit, Democratic Republic of the Congo], 1995."Journal of Infectious Diseases 179.Supplement 1 (1999): S87-S91. To determine if a given outbreak follows the same epidemic chain, sequencing of the virus can be performed to find out, which strain the patient was infected with. If the virus within each patient differs drastically, it have been inferred that all of the patients were infected from different sources. Each source should contain a genetically different strain of Ebola because the virus evolved independently in each host before being transmitted. As with any virus, Ebola can rapidly evolve making the development of antiviral treatments extremely difficult. However, understanding the specific mechanism behind the Ebola evolution could make it easier to improve medical treatment. Suzuki ''et al. ''attempted to quantify the mutation rate of Ebola compared to other types of diseases. Suzuki, Yoshiyuki, and Takashi Gojobori. "[http://mbe.oxfordjournals.org/content/14/8/800.short The origin and evolution of Ebola and Marburg viruses]." Molecular biology and evolution 14.8 (1997): 800-806. They found that Ebola evolved about one hundred times slower than influenza A, but was on the same order of magnitude of hepatitis B. Screening for the Virus To control the spread of Ebola (and other viruses), rapid screening techniques have been developed to quickly test if someone is positive for the disease. Drosten, Christian, et al. "[http://jcm.asm.org/content/40/7/2323.short Rapid detection and quantification of RNA of Ebola and Marburg viruses, Lassa virus, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, dengue virus, and yellow fever virus by real-time reverse transcription-PCR]." Journal of clinical microbiology 40.7 (2002): 2323-2330. The advantage to a rapid screening technique is two-fold. This method is very effective at getting very accurate results very quickly. Also, more people can be screened if the process is fast and if the process is not an inconvenience, it would be simple to set up check points near areas of high Ebola incidence to prevent the spread of the disease. One method that meets both of these criteria is real-time reverse transcriptase polymerase chain reaction (PCR). It involves the typical steps of PCR (e.g. designing primers, amplification of RNA, etc.), but Drosten ''et al.'' have developed a technique to read the sequence of the PCR product in real time during amplification. This process allows for Ebola screenings to be done in ~3 hours, making it a great improvement over traditional methods that must first run the PCR reaction and then run the sequencing reaction later. Now, both reactions happen in parallel cutting the required time by more than half. However, there is one challenge with real-time reverse transcriptase PCR in this circumstance. The problem arises due to the high mutation rate associated with viruses. The primers designed for reverse transcriptase binding can become dysfunctional over time due to mutations in the viral RNA. More specifically, if there is a mutation in the viral genome at the site where the PCR primer is supposed to bind, it is possible that the PCR reaction will fail, yielding a false negative. If is for this reason that control experiments need to be performed frequently to ensure that the most recent strain of the virus has not mutated to the point where the designed primers are obsolete and the virus is unrecognizable by current rapid-screening methods. Developing a Vaccine Currently there is an experimental vaccine being rushed into development and tested in humans. Cohen, Jon. "[http://www.sciencemag.org/content/345/6202/1228.short Ebola vaccines racing forward at record pace]." Science 345.6202 (2014): 1228-1229. Testing will be carried out in four African countries to determine the efficacy of the vaccine. Unfortunately, even with such strong efforts, vaccine production will not be high enough to make a dent in the Ebola outbreak until around June 2015. The sudden acceleration of the number of Ebola outbreaks coupled with the severity of the recent cases has made developing a vaccine and other effective treatments a high international priority. References